An Randomized Double Blind Controlled Trial of niPGT-A in Women With RPL

NCT05685147 | Not Yet Recruiting

• 1 other identifier: niPGTAinRPL
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: To compare the efficacy in embryo selection based on morphology alone compared to morphology and non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) in women with recurrent pregnancy loss (RPL) undergoing in vitro fertilization (IVF). Hypothesis to be tested: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with that based on morphology alone. Design and subjects: Randomized double-blind randomized controlled trial. Women with RPL undergoing IVF will be enrolled. Interventions: Spent culture medium (SCM) of each blastocyst will be frozen individually. They will be randomly allocated into two groups: (1) the intervention group based on morphology and niPGT-A and (2) the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of SCM will be replaced first. Main outcome measures: The primary outcome is the miscarriage rate per the first embryo transfer. Data analysis: Comparison of quantitative variables will be performed using Student's t, while categorical variables will be compared using a Chi-square analysis. All statistical analyses will be performed with the intention to treat and per protocol, and a p-value \<0.05 will be considered statistically significant. Expected outcome results: The embryo selection based on morphology and niPGT-A results in a lower miscarriage rate and a higher live birth rate in IVF as compared with the control group based on morphology alone.

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

• Miscarriage rate

  Miscarriage rate in the first FET and is defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy. • Miscarriage rate in the first FET and is defined as a clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.

  12 weeks

Secondary Outcomes (18)

• Live birth

  1 year

• positive urine pregnancy test

  at 2 weeks after embryo tranfer

• Clinical pregnancy

  6 weeks

• Ongoing pregnancy

  10 weeks

• Multiple pregnancy

  more than one intrauterine sac at 6-8 weeks

Study Arms (2)

Intervention group

EXPERIMENTAL

the intervention group using morphology and niPGT-A

Genetic: Non-invasive Preimplantation genetic testing for aneuploidy status

Control group

NO INTERVENTION

the control group based on morphology alone.

Interventions

Non-invasive Preimplantation genetic testing for aneuploidy status GENETIC

In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. Sequence of replacement shall be altered by the NiPGT result after morpholgy.

Intervention group

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged less than 40 years at the time of ovarian stimulation and
• \>=two spontaneous miscarriages in the first trimester
• Unexplained recurrent pregnancy loss after standard investigation
• At least one blastocyst available on day 5 or 6 after the retrieval.

You may not qualify if:

• Women undergoing PGT for monogenic diseases or structural rearrangement of chromosomes;
• Use of donor oocytes;
• Hydrosalpinx shown on pelvic scanning and not surgically treated
• Uterine anomalies distorting the uterine cavity in three dimensional ultrasound
• No usable blastocysts on day 5 or 6 after the retrieval

Sponsors & Collaborators

• Queen Mary Hospital, Hong Kong: lead

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

Location

Related Publications (12)

• van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012 Dec;1822(12):1951-9. doi: 10.1016/j.bbadis.2012.07.001. Epub 2012 Jul 13.

  PMID: 22796359 RESULT

• Spandorfer SD, Davis OK, Barmat LI, Chung PH, Rosenwaks Z. Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril. 2004 May;81(5):1265-9. doi: 10.1016/j.fertnstert.2003.09.057.

  PMID: 15136087 RESULT

• Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen A, Vidal C, Giles J, Ferrando M, Cabanillas S, Remohi J, Pellicer A, Simon C. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017 May;107(5):1122-1129. doi: 10.1016/j.fertnstert.2017.03.011. Epub 2017 Apr 19.

  PMID: 28433371 RESULT

• Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.

  PMID: 25432917 RESULT

• Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M, Wells D, Gordon T, Stock-Myer S, Willman S; STAR Study Group. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019 Dec;112(6):1071-1079.e7. doi: 10.1016/j.fertnstert.2019.07.1346. Epub 2019 Sep 21.

  PMID: 31551155 RESULT

• Assou S, Ait-Ahmed O, El Messaoudi S, Thierry AR, Hamamah S. Non-invasive pre-implantation genetic diagnosis of X-linked disorders. Med Hypotheses. 2014 Oct;83(4):506-8. doi: 10.1016/j.mehy.2014.08.019. Epub 2014 Aug 23.

  PMID: 25182520 RESULT

• Xu J, Fang R, Chen L, Chen D, Xiao JP, Yang W, Wang H, Song X, Ma T, Bo S, Shi C, Ren J, Huang L, Cai LY, Yao B, Xie XS, Lu S. Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11907-11912. doi: 10.1073/pnas.1613294113. Epub 2016 Sep 29.

  PMID: 27688762 RESULT

• Shamonki MI, Jin H, Haimowitz Z, Liu L. Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media. Fertil Steril. 2016 Nov;106(6):1312-1318. doi: 10.1016/j.fertnstert.2016.07.1112. Epub 2016 Aug 24.

  PMID: 27565258 RESULT

• Feichtinger M, Vaccari E, Carli L, Wallner E, Madel U, Figl K, Palini S, Feichtinger W. Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study. Reprod Biomed Online. 2017 Jun;34(6):583-589. doi: 10.1016/j.rbmo.2017.03.015. Epub 2017 Mar 28.

  PMID: 28416168 RESULT

• Ho JR, Arrach N, Rhodes-Long K, Ahmady A, Ingles S, Chung K, Bendikson KA, Paulson RJ, McGinnis LK. Pushing the limits of detection: investigation of cell-free DNA for aneuploidy screening in embryos. Fertil Steril. 2018 Aug;110(3):467-475.e2. doi: 10.1016/j.fertnstert.2018.03.036. Epub 2018 Jun 28.

  PMID: 29960707 RESULT

• Capalbo A, Romanelli V, Patassini C, Poli M, Girardi L, Giancani A, Stoppa M, Cimadomo D, Ubaldi FM, Rienzi L. Diagnostic efficacy of blastocoel fluid and spent media as sources of DNA for preimplantation genetic testing in standard clinical conditions. Fertil Steril. 2018 Oct;110(5):870-879.e5. doi: 10.1016/j.fertnstert.2018.05.031.

  PMID: 30316433 RESULT

• Hiby SE, Regan L, Lo W, Farrell L, Carrington M, Moffett A. Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod. 2008 Apr;23(4):972-6. doi: 10.1093/humrep/den011. Epub 2008 Feb 8.

  PMID: 18263639 RESULT

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Ernest HY Ng

  The University of Hong Kong

  STUDY DIRECTOR

Central Study Contacts

Heidi Cheng, MBBS

CONTACT

852-22553657; chy610a@ha.org.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The embryologist will grade the morphology of blastocysts according to Gardner's criteria stated above and enter the grading of blastocysts into an online database, which will be managed by an IT technician. The laboratory staff in the PGT laboratory will enter the PGT result into a local database when the NIPGT results are available. The IT technician will collect the database from the PGT laboratory and enter it into the online software to compile the sequence of embryo transfer according to a pre-determined algorithm which depends on the day of blastocyst development (day 5 better than day 6), blastocyst morphology and niPGT-A result. The IT technician will issue the sequence of embryo transfer which does not contain information on the grading of the blastocyst and the NIPGT result to the embryologists in the IVF laboratory. Therefore, the subjects recruited, the clinicians and the embryologists will be blinded to the group allocation.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Consultant

Study Record Dates

• First Submitted: January 2, 2023
• First Posted: January 13, 2023
• Study Start: July 1, 2023
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2026
• Last Updated: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)